Estimating the Precision of Exact Mass Measurements on an Orthogonal Time-of-Flight Mass Spectrometer

128

The applicability of ultra-performance liquid chromatography (UPLC) combined with fullscan accurate mass time-of-flight (TOF) and Orbitrap mass spectrometry (MS) to the analysis of hormone and veterinary drug residues was evaluated. Extracts from blank bovine hair were fortified with 14 steroid esters. UPLC-Orbitrap MS performed at a resolving power of 60,000 (FWHM) enabled the detection and accurate mass measurement (Ͻ3 ppm error) of all 14 steroid esters at low ng/g concentration level, despite the complex matrix background. A 5 ppm mass tolerance window proved to be essential to generate highly selective reconstructed ion chromatograms (RICs) having reduced background from the hair matrix. UPLC-Orbitrap MS at a lower resolving power of 7500 and UPLC-TOFMS at mass resolving power 10,000 failed both to detect all of the steroid esters in hair extracts owing to the inability to mass resolve analyte ions from co-eluting isobaric matrix compounds. In a second application, animal feed extracts were fortified with coccidiostats drugs at levels ranging from 240 to 1900 ng/g. UPLC-Orbitrap MS conducted at a resolving power of 7500 and 60,000 and UPLC-TOFMS detected all of the analytes at the lowest investigated level. Thanks to the higher analyte-to-matrix background ratio, the utilization of very narrow mass tolerance windows in the RIC was not required. This study demonstrates that even when the targeted sample preparation from conventional LC-MS/MS is applied to UPLC with full-scan accurate mass MS, false compliant (false negative) results can be obtained when the mass resolving power of the MS is insufficient to separate analyte ions from isobaric co-eluting sample matrix ions. The current trend towards more generic and less selective sample preparation is expected to aggravate this issue further. (J Am Soc Mass Spectrom 2009, 20, 451-463)

Section: General Considerations Of Precision and Accuracy Of Mass Measupporting

confidence: 88%

Full-scan accurate mass selectivity of ultra-performance liquid chromatography combined with time-of-flight and orbitrap mass spectrometry in hormone and veterinary drug residue analysis

Heeft¹,

Bolck²,

Beumer³

et al. 2009

128

“…Although the accuracy of mass measurement on a Q-TOF should be ϳ5 ppm with an internal calibrant, we found the accuracy depends significantly on the signal intensity°ratio°for°the°target°and°the°calibrant° [9].°With an increasing concentration of the target compound at a fixed concentration of the calibrant, the measured difference in m/z increased as that of the analyte shifted to a lower value compared to that of the calibrant. A decreasing concentration of target gave, on the other hand, a decreasing difference between the m/z values of the analyte and its internal standard.…”

Section: Resultsmentioning

confidence: 84%

“…Their mass measurement precision/accuracy can be Ϯ5 ppm when a mass calibrant [8,9] is cointroduced by various methods [10 -12]. When interfaced to a quadrupole (QTOF), accurate mass measurement in the MS/MS mode is even possible [8].…”

mentioning

confidence: 99%

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Correction of accurate mass measurement for target compound verification by quadrupole time-of-flight mass spectrometry

Köfeler

Gross

2005

The aim of this work is to evaluate quadrupole/time-of-flight (QTOF) mass spectrometry for simultaneous measurement of accurate mass and quantification of a target by using a stable isotopically labeled internal standard. Mixtures of caffeine and 13 C 3 -caffeine (internal standard) at different concentration ratios were analyzed by capillary HPLC/QTOF. A calibration plot for quantification is linear over a factor of 20. Without invoking any correction scheme, the mass accuracy seriously degraded when the ratio of the mass standard to the test compound was not unity. The accuracy could be restored to approximately 2 ppm by using a quadratic function to correct the measured mass as a function of the measured signal ratio of target and internal calibrant. (J Am Soc Mass Spectrom 2005, 16, 406 -408)

“…Wolff et al achieved mass measurement accuracy to within 5 mDa for ions in the m/z range 74 to 423 [16]. Blom has also demonstrated mass measurement accuracy of Ͻ3 ppm when using a quadrupole-TOF in conjunction with a Z-Spray source [17]. Mass accuracy of better than 2 ppm has been demonstrated by Richards when using a quadrupole-TOF mass spectrometer.…”

mentioning

confidence: 99%

Intercomparison study on accurate mass measurement of small molecules in mass spectrometry

Bristow¹,

Webb²

2003

114

The results from an intercomparison of accurate mass measurement of a small molecule (molecular weight 475 Da) across a broad range of mass spectrometers are reported. The intercomparison was designed to evaluate the relative capabilities and the optimum methodology of the diverse range of mass spectrometers currently used to record accurate mass measurements. The data will be used as a basis for developing guidance on accurate mass measurement. The need for guidance has resulted from the continued growth in the use of accurate mass measurements for assignment of elemental formula in the chemical and biochemical industries. This has been fuelled by a number of factors and includes the rapid pace of instrument development, which has enabled accurate mass measurements to be made in a less costly, yet robust fashion. The data from the intercomparison will allow us to compare those protocols that produced excellent accuracy and precision with those that produced poorer accuracy and/or precision for each type of mass spectrometer. The key points for best practice will then be established from this comparison for each type of mass spectrometer and accurate mass measurement technique. A compound was sent to the participating laboratories (in the UK, Europe, and USA), the identity of which was not revealed. Each laboratory was asked to record a minimum of five repeat mass measurements of the molecular species using their local protocols and their preferred ionization technique or techniques. To the best of our knowledge there were no interfering (unresolved) ions that originated from the sample. A questionnaire was also completed with the experimental work. The information from the questionnaires was used to evaluate the protocols used to record the measurements. Forty-five laboratories have reported their results. To summarize the performance of mass spectrometers in the intercomparison, magnetic sector field mass spectrometers used in peak matching mode and FTMS reported the highest mean mass measurement accuracy (88 and 83%, respectively, achieved Յ1 ppm). Magnetic sector field mass spectrometers used in voltage scanning produced 60% of the mean mass measurements with accuracy Յ1 ppm. Magnetic sector field mass spectrometers used in magnet scanning modes, quadrupole-TOF and TOF instruments generally achieved mean mass measurement accuracy between 5 and 10 ppm. The two low resolution triple quadrupoles used in the inter-comparison produced mean mass measurement accuracy of Ͻ2 ppm. The precision of the data from each instrument and experiment type is an important consideration when evaluating their relative capabilities. Using both the precision and accuracy, it will be possible to define the uncertainty associated with the elemental formulae derived from accurate mass measurements. Therefore, a thorough statistical evaluation of the data is underway and will be presented in a subsequent publication. A ccurate mass measurement of small molecules is used to determine elemental formulae. The better the accuracy the less ...